Sulfiredoxin (Srx) is a novel gene that has been found to be highly expressed in several types of human cancers including cancers of skin and lung. However, the function of Srx in cancer development has not been well studied. The primary hypothesis of this study is that Srx has an oncogenic function that may contribute to tumorigenesis and cancer progression in mouse and human. The long-term object of this study is to understand the function and molecular mechanisms of Srx in human cancer development and progression, which will be valuable for future development of novel strategies for cancer prevention and treatment. The first aim of the study is to test whether the genomic loss of Srx will cause mice more resistant to tumorigenesis using a chemical induced mouse skin carcinogenesis model. The second aim is to study the function and molecular basis of Srx in human lung cancer cell migration, invasion and metastasis. The third aim is to characterize the proteins that interact with Srx and to determine how they contribute to the oncogenic function of Srx in human lung cancer cells. The function of Srx will be examined using cell culture and mouse model of skin carcinogenesis, and mouse models of human cancer cell tumorigenesis and metastasis. The mechanistic study will be focused on the cell signaling change and protein-protein interactions using biochemistry and molecular biology techniques. The successful completion of the proposed research will further the understanding of the role of Srx in human cancer, will broaden the knowledge of antioxidant proteins in tumorigenesis and cancer progression, and will facilitate the development of novel strategies for cancer prevention and treatment.